Journal of Biomolecular Structure & Dynamics最新文献_第6页

An integrated bioinformatics approach to early diagnosis, prognosis and therapeutics of non-small-cell lung cancer. 非小细胞肺癌早期诊断、预后和治疗的综合生物信息学方法。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-11-13 DOI: 10.1080/07391102.2024.2425840

Adiba Sultana, Md Shahin Alam, Alima Khanam, Yuxin Lin, Shumin Ren, Rajeev K Singla, Rohit Sharma, Kamil Kuca, Bairong Shen

{"title":"An integrated bioinformatics approach to early diagnosis, prognosis and therapeutics of non-small-cell lung cancer.","authors":"Adiba Sultana, Md Shahin Alam, Alima Khanam, Yuxin Lin, Shumin Ren, Rajeev K Singla, Rohit Sharma, Kamil Kuca, Bairong Shen","doi":"10.1080/07391102.2024.2425840","DOIUrl":"https://doi.org/10.1080/07391102.2024.2425840","url":null,"abstract":"Non-small-cell lung cancer (NSCLC) is one of the most deadly tumors characterized by poor survival rates. Advances in therapeutics and precise identification of biomarkers can potentially reduce the mortality rate. Thus, this study aimed to identify a set of common and stable gene biomarkers through integrated bioinformatics approaches that might be effective for NSCLC early diagnosis, prognosis, and therapies. Four gene expression profiles (GSE19804, GSE19188, GSE10072, and GSE32863) downloaded from the Gene Expression Omnibus database to identify common differential expressed genes (DEGs). A total of 213 overlapping DEGs (oDEGs) between NSCLC and healthy samples were identified by using statistical LIMMA method. Then 6 common top-ranked key genes (KGs) (CENPF, CAV1, ASPM, CCNB2, PRC1, and KIAA0101) were selected by using four network-measurer methods in the protein- protein interaction network. The GO functional and KEGG pathway enrichment analysis were performed to reveal some significant functions and pathways associated with NSCLC progression. Transcriptional and post-transcriptional factors of KGs were identified through the regulatory interaction network. The prognostic power and expression level of KGs were validated by using the independent data through the Kaplan-Meier and Box plots, respectively. Finally, 4 KGs-guided repositioning candidate drugs (ZSTK474, GSK2126458, Masitinib, and Trametinib) were proposed. The stability of three top-ranked drug-target interactions (CAV1 vs. ZSTK474, CAV1 vs. GSK2126458, and ASPM vs. Trametinib) were investigated by computing their binding free energies for 140 ns MD-simulation based on MM-PBSA approach. Therefore, the findings of this computational study may be useful for early prognosis, diagnosis and therapies of NSCLC.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting mitochondrial dynamics: an in-silico approach for repurposing antifungal drugs in OSCC treatment. 以线粒体动力学为靶点：一种在OSCC治疗中重新使用抗真菌药物的分子内方法。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-11-12 DOI: 10.1080/07391102.2024.2425831

Rohith Raali, Neha Sivakumar, Harsh Vardhan J, Suresh P K

{"title":"Targeting mitochondrial dynamics: an in-silico approach for repurposing antifungal drugs in OSCC treatment.","authors":"Rohith Raali, Neha Sivakumar, Harsh Vardhan J, Suresh P K","doi":"10.1080/07391102.2024.2425831","DOIUrl":"https://doi.org/10.1080/07391102.2024.2425831","url":null,"abstract":"Drug repurposing for cancer treatment is a valuable strategy to identify existing drugs with known safety profiles that could combat the neoplasm, by reducing costs. Oral squamous cell carcinoma, an ulcer-proliferative lesion on the mucosal epithelium, is the most common oral malignancy. About 10% of cancer patients within the Indian subcontinent suffer from OSCC, primarily due to chewing of betel plant derivatives. Concomitant administration of the chemotherapeutic agent (Cisplatin/Paclitaxel) is the treatment of choice. Analysis of the oral mycobiome of OSCC patients has projected the role of Candida albicans in potentiating OSCC. Hence, repurposing antifungal drugs emerges as a promising approach, as these drugs could target both the cancer cells and the infection. Cancer cells often have heightened energy requirements, and targeting mitochondrial proteins to disrupt mitochondrial division and induce dysfunction contributing to cell death, offers a method for treating OSCC. We identified 18 mitochondrial targets playing a crucial role in the maintenance of mitochondrial homeostasis. They were docked against 125 antifungal ligand molecules sourced from PUBCHEM. Ligand profiling was performed using Lipinski's rule of 5, SwissADME and ProTox. Also, molecular dynamics and MM-PBSA were performed to validate our results. Among all protein ligand interactions, we observed that targeting DRP1 with itraconazole yielded superior binding and stability. Overall, lower toxicity and thumping ADME properties solidified the choice of ligand. We hope this experimental approach will enable us to provide a basis for selecting a lead molecule for a possible novel nano-formulation and validate our finding through in-vitro cell line-based testing.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Screening and design of PARP12 inhibitors from traditional Chinese medicine small molecules using computational modeling and simulation. 利用计算建模和模拟从中药小分子中筛选和设计 PARP12 抑制剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-11-11 DOI: 10.1080/07391102.2024.2424941

Xiaochen Yang, Baolin Liu, Aamir Mehmood, Daixi Li

{"title":"Screening and design of PARP12 inhibitors from traditional Chinese medicine small molecules using computational modeling and simulation.","authors":"Xiaochen Yang, Baolin Liu, Aamir Mehmood, Daixi Li","doi":"10.1080/07391102.2024.2424941","DOIUrl":"https://doi.org/10.1080/07391102.2024.2424941","url":null,"abstract":"The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a pivotal role in orchestrating a multitude of cellular processes, including DNA repair mechanisms, transcriptional regulation, and modulation of immune responses. Within this family, PARP12 emerges as a noteworthy candidate for targeted cancer therapeutics. Consequently, this investigation endeavors to screen and design potential PARP12 inhibitors derived from traditional Chinese medicinal compounds by employing sophisticated molecular modeling and computational medicinal chemistry approaches. The compound RBN2397 is utilized as a benchmark, and the binding efficacies of the newly identified small molecules are assessed against a spectrum of criteria, encompassing molecular interactions, binding free energy, and extensive post-simulation analyses. The outcomes demonstrated that the identified small molecules, specifically tcm8650 and its derivative XC-1, possess remarkable binding affinities and exhibit reduced binding free energies compared to RBN2397. The molecular docking and interaction profiles of these compounds were also comprehensively scrutinized. Moreover, ADMET profiling meticulously evaluated the pharmacokinetic profiles and physicochemical characteristics of these promising molecules and their projected human physiological impact. These computational studies indicated their potential therapeutic applicability and predicted acceptable safety profile, advocating their further exploration as viable candidates in cancer treatment.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential mechanism of Laportea bulbifera on treating inflammation and tumor via metabolomics, network pharmacology and molecular docking. 通过代谢组学、网络药理学和分子对接研究发现球叶木贼治疗炎症和肿瘤的潜在机制

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-11-10 DOI: 10.1080/07391102.2024.2426077

Zhan Feng, Yan Zheng, Jin Pei, Linfang Huang

{"title":"Potential mechanism of Laportea bulbifera on treating inflammation and tumor via metabolomics, network pharmacology and molecular docking.","authors":"Zhan Feng, Yan Zheng, Jin Pei, Linfang Huang","doi":"10.1080/07391102.2024.2426077","DOIUrl":"https://doi.org/10.1080/07391102.2024.2426077","url":null,"abstract":"This study aimed to utilize metabolomics, network pharmacology, and molecular docking techniques to identify the major active components of Laportea bulbifera and investigate their anti-inflammatory and potential anti-tumor mechanisms. The metabolic constituents of L. bulbifera were examined utilizing UPLC-ESI-MS/MS. PPI networks and compound-target-pathway networks were established using resources such as TCMSP, Swiss Target Prediction, DAVID, STRING database, and Cytoscape software. Molecular docking analysis of the most important compounds and targets was conducted using Autodock4, followed by validation of the molecular docking results' stability using GROMACS. The UPLC-ESI-MS/MS analysis identified a total of 798 compounds. A network pharmacology-based analysis was conducted, revealing that eight compounds and four molecular targets-namely, TNF, IL6, PIK3CA, and HDAC1-were enriched in the network. Pathway analysis of the identified targets demonstrated enrichment in 217 KEGG pathways. Molecular docking analysis and molecular dynamics simulations demonstrated strong therapeutic potential of N-feruloyltyramine, N-feruloylagmatine, and Ellagic acid against various inflammatory and tumor diseases. This study, for the first time, employed an integrated strategy of metabolomics, network pharmacology, molecular docking, and molecular dynamics, elucidating the mechanisms underlying the anti-inflammatory and potential anti-tumor effects of L. bulbifera, laying the foundation for subsequent drug development endeavors.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering significant interaction between Clp1 (CF IA) and Ssu72 (CPF) in pre-mRNA processing via in silico approaches. 通过硅学方法解密 Clp1（CF IA）和 Ssu72（CPF）在前 mRNA 处理过程中的重要相互作用。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-11-10 DOI: 10.1080/07391102.2024.2426757

Mandeep Kaur, Prakhar Agrawal, Gurpal Singh, Ganesan Senthil Kumar, Ravi Pratap Barnwal

{"title":"Deciphering significant interaction between Clp1 (CF IA) and Ssu72 (CPF) in pre-mRNA processing via in silico approaches.","authors":"Mandeep Kaur, Prakhar Agrawal, Gurpal Singh, Ganesan Senthil Kumar, Ravi Pratap Barnwal","doi":"10.1080/07391102.2024.2426757","DOIUrl":"https://doi.org/10.1080/07391102.2024.2426757","url":null,"abstract":"The cleavage and polyadenylation step are indispensable for pre-mRNA processing in eukaryotes. Defective 3'- end maturation of precursor mRNA has catastrophic effects, leading to several diseases in humans. This processing is orchestrated by a complex machinery comprising more than 20 proteins in Saccharomyces cerevisiae. Endonucleolytic cleavage followed by the addition of poly(A) tail at the 3'-end of the precursor mRNA requires CPF, CF IA and CF IB proteins. Clp1, a protein factor of the CF IA sub-unit is indispensable for the functioning of this machinery. Based on in silico analysis including molecular docking via different docking servers and molecular dynamics (MD) simulations, the current study provides key evidence of the Clp1 N-terminal (1-100 amino acids) domain's interaction with Ssu72. MD simulations consolidate this binding between Clp1 and Ssu72. Our study presents strong evidence of a model where Clp1 (CF IA) associates with Ssu72 (CPF) and both the proteins are vital for tethering the complex for mediating cleavage and polyadenylation reaction during the key events of pre-mRNA 3'-end processing. These findings may pave the way to decipher the individual roles of Clp1 and Ssu72 during pre-mRNA maturation.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural and functional consequences of non-synonymous SNPs within the LAMA2 protein: a molecular dynamics perspective. LAMA2 蛋白中非同义 SNP 的结构和功能后果：分子动力学视角。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-11-10 DOI: 10.1080/07391102.2024.2426756

Rafat Ali, Armiya Sultan, Romana Ishrat, Deeksha Saini, Shaheen Hayat, Nida Jamil Khan

{"title":"Structural and functional consequences of non-synonymous SNPs within the LAMA2 protein: a molecular dynamics perspective.","authors":"Rafat Ali, Armiya Sultan, Romana Ishrat, Deeksha Saini, Shaheen Hayat, Nida Jamil Khan","doi":"10.1080/07391102.2024.2426756","DOIUrl":"https://doi.org/10.1080/07391102.2024.2426756","url":null,"abstract":"Clinical phenotypic presentations associated with LAMA2 deficiency have shown a variety of manifestations. LAMA2 mutations are mainly linked to congenital muscular dystrophy, but there is also mounting evidence suggesting their presence in inflammatory breast cancer, laryngopharyngeal squamous cell carcinoma, and ventricular tachycardia related to coronary artery disease and cardiomyopathy. This study examined the structural and functional impacts of 144 non-synonymous single nucleotide polymorphisms (nsSNPs) within the LAMA2 gene. Through multi-tiered sequence and structure-based methods, 11 deleterious and destabilizing mutations were identified (A1362T, E1308Q, E1360G, I1276S, L1195P, M1359T, P1232H, P1238A, P1272L, Y1234H, Y1338C). Further, four mutations (L1195P, Y1234H, P1238A, A1362T), which aligned with conserved positions, were subjected to 500 ns molecular dynamics (MD) simulations. RMSD calculated from MD trajectories highlighted structural disparities between wild-type and mutant forms, with the latter showing greater flexibility. Radius of gyration analysis indicated reduced compactness, solvent accessibility changes suggested unfolding, and hydrogen bond (HB) analysis demonstrated disrupted integrity. The HB analysis revealed disruptions in structural integrity due to diminished hydrogen bonds in mutants. Secondary structure analysis revealed significant alterations in secondary structural content. Principal Component Analysis unveiled increased dynamic behavior in mutants. Gibbs free energy landscape analysis reflected distinct energy minima regions in mutants, indicating structural destabilization. Overall, this study revealed the functional and structural ramifications of nsSNPs in the LAMA2 gene, providing valuable insights into potential disease-causing mutations and warranting future research on understanding LAMA2 associated diseases and disorders.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational screening of phytocompounds from C. amboinicus identifies potential inhibitors of influenza A (H3N2) virus by targeting hemagglutinin. 通过对 C. amboinicus 植物化合物的计算筛选，确定了针对血凝素的甲型 H3N2 流感病毒潜在抑制剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-11-09 DOI: 10.1080/07391102.2024.2424940

Kadabagere Narayanaswamy Hemavathi, Sushil Kumar Middha, Rajesh Raju, Rajendra Pilankatta, Thottethodi Subrahmanya Keshava Prasad, Chandran S Abhinand

{"title":"Computational screening of phytocompounds from C. amboinicus identifies potential inhibitors of influenza A (H3N2) virus by targeting hemagglutinin.","authors":"Kadabagere Narayanaswamy Hemavathi, Sushil Kumar Middha, Rajesh Raju, Rajendra Pilankatta, Thottethodi Subrahmanya Keshava Prasad, Chandran S Abhinand","doi":"10.1080/07391102.2024.2424940","DOIUrl":"https://doi.org/10.1080/07391102.2024.2424940","url":null,"abstract":"The H3N2 subtype of the influenza A virus continues to be a notable public health issue due to its association with seasonal epidemics and severe human morbidity. The constrained effectiveness of current antiviral medications, combined with the inevitable emergence of drug-resistant variants, mandates the exploration of innovative therapeutic approaches. This study focuses on the identification of phytocompounds from Coleus amboinicus with the potential to target hemagglutinin, viral protein involved in viral entry by binding to sialyl glycoconjugates receptors on the surface of host cells. Molecular docking studies were carried out to assess the efficacy of C. amboinicus phytocompounds with hemagglutinin receptor-binding site. The study revealed that among the 84 signature phytocompounds, isosalvianolic acid and salvianolic acid C showed the highest docking scores and favourable intermolecular interactions. Pharmacokinetic analysis and Pan-assay interference compounds (PAINS) filtering confirmed that isosalvianolic acid meets the criteria outlined in Lipinski's rule of five, exhibits favourable ADMET profiles and passes PAINS filters. Furthermore, the molecular dynamics simulations followed by radius of gyration (Rg), solvent accessible surface area (SASA), and MM-PBSA calculations for binding free energy, verified the stability of the docked complexes. Together, the study identifies isosalvianolic acid as a promising inhibitor of the H3N2 virus by binding to hemagglutinin, indicating its potential as a strategy for therapeutic intervention.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular docking and molecular dynamics of hypoxia-inducible factor (HIF-1alpha): towards potential inhibitors. 低氧诱导因子（HIF-1alpha）的分子对接和分子动力学：寻找潜在的抑制剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-11-09 DOI: 10.1080/07391102.2024.2425839

Dina Reda, Abdo A Elfiky, M Elnagdy, Magdy M Khalil

{"title":"Molecular docking and molecular dynamics of hypoxia-inducible factor (HIF-1alpha): towards potential inhibitors.","authors":"Dina Reda, Abdo A Elfiky, M Elnagdy, Magdy M Khalil","doi":"10.1080/07391102.2024.2425839","DOIUrl":"https://doi.org/10.1080/07391102.2024.2425839","url":null,"abstract":"HIF-1α is a primary regulator in the adaptation of cancer cells to hypoxia. The aim was to find out new inhibitors of the HIF-1α. A molecular dynamic (MD) simulation performed on HIF-1α showed stable dynamic features. Virtual screening of 217 anticancer drugs was performed along with a positive control (2-Methoxyestradiolm, 2-ME2) on an optimized HIF-1α and dynamically simulated structure. Docking results produced two compounds namely pycnidione and nilotinib of high binding affinity -9.34 kcal/mol and -9.04 kcal/mol respectively, whereas 2-ME2 displayed a relatively lower affinity (-6.68 kcal/mol). For the three complexes, MD of 200 ns simulation was run. Data analysis showed that the three medications behaved similarly in the MD simulation. Nilotinib had a lower RMSD and higher SASA than the other complexes. In addition, the Nilotinib-HIF-1α combination had a lower RMSF value, a flatter Rg, and a number of hydrogen bonds similar to other complexes. MM-GBSA analysis revealed that nilotinib, pycnidione and 2-ME2 compounds had free binding energy of -23.77 ± 5.29, -21.85 ± 4.24 and -7.53 ± 6.62 kcal/mol respectively. Nilotinib and pycnidione bind competitively to HIF-1α, with nilotinib showing consistent molecular-dynamic properties. They relatively pass the blood-brain barrier, non-carcinogenic, and have IV-category acute oral toxicity. They have low CYP inhibitory characteristics. Further investigations are therefore warranted to elucidate their implications in hypoxia pathways, cell proliferation, apoptosis, survival, and metastatic potential.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-20"},"PeriodicalIF":2.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TOLEDO: enhancing Maestro GUI for non-expert users to perform massive MD simulations. TOLEDO：增强 Maestro 图形用户界面，方便非专业用户执行大规模 MD 仿真。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-11-05 DOI: 10.1080/07391102.2024.2423380

Miguel Carmena-Bargueño, Carlos Martínez-Cortés, Antonio Jesús Banegas-Luna, Horacio Pérez-Sánchez

{"title":"TOLEDO: enhancing Maestro GUI for non-expert users to perform massive MD simulations.","authors":"Miguel Carmena-Bargueño, Carlos Martínez-Cortés, Antonio Jesús Banegas-Luna, Horacio Pérez-Sánchez","doi":"10.1080/07391102.2024.2423380","DOIUrl":"https://doi.org/10.1080/07391102.2024.2423380","url":null,"abstract":"Classical Molecular Dynamics (MD) simulates the dynamical evolution of biological systems at the atomic level. Using MD in conjunction with high-performance computing (HPC) architectures, we can evaluate the possible interactions between a ligand library against one protein target to find a drug that can influence a protein target to cure a disease. Simultaneously, we can also obtain information about their dynamic evolution. One of the primary software packages for MD simulations is Desmond, which employs Maestro for the setup, execution, and analysis of MD through a graphical user interface (GUI), which is suitable even for non-expert users. However, using the GUI, users can typically run only one short (less than 1000 ns) MD each time. Our work aims to create a method/protocol to run several MD simulations simultaneously on a remote HPC cluster within Maestro-Desmond. In this work, we provide TOLEDO (Throughput Optimization of Ligand-Protein Systems Exploration through Dynamics simulation in Optimized HPC systems) to overcome such limitations and run several MD simulations simultaneously. The best feature of TOLEDO is its independence from the usual time constraints of many clusters, with storage space being the only limitation. To run TOLEDO, we prepare/set up the protein-ligand complex before running MD via Maestro GUI. Next, we run the main TOLEDO script for several MD simulations on a supercomputer. When TOLEDO finishes, users obtain reports and graphics. The obtained results are easily interpretable. In essence, TOLEDO significantly enhances MD throughput beyond the capabilities of the Maestro GUI.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oleanolic acid purified from the stem bark of Olax subscorpioidea Oliv. inhibits the function and catalysis of human 17β-hydroxysteroid dehydrogenase 1. 从Olax subscorpioidea Oliv.茎皮中提纯的齐墩果酸能抑制人类17β-羟基类固醇脱氢酶1的功能和催化作用。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-11-01 DOI: 10.1080/07391102.2024.2423173

Yemi A Adekunle, Babatunde B Samuel, Wande M Oluyemi, Adeniyi T Adewumi, Salerwe Mosebi, Lutfun Nahar, Amos A Fatokun, Satyajit D Sarker

{"title":"Oleanolic acid purified from the stem bark of Olax subscorpioidea Oliv. inhibits the function and catalysis of human 17β-hydroxysteroid dehydrogenase 1.","authors":"Yemi A Adekunle, Babatunde B Samuel, Wande M Oluyemi, Adeniyi T Adewumi, Salerwe Mosebi, Lutfun Nahar, Amos A Fatokun, Satyajit D Sarker","doi":"10.1080/07391102.2024.2423173","DOIUrl":"https://doi.org/10.1080/07391102.2024.2423173","url":null,"abstract":"Cancer is a leading cause of global death. Medicinal plants have gained increasing attention in cancer drug discovery. In this study, the stem bark extract of Olax subscorpioidea, which is used in ethnomedicine to treat cancer, was subjected to phytochemical investigation leading to the isolation of oleanolic acid (OA). The structure was elucidated by 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopic (NMR) data, and by comparing its data with previously reported data. Molecular docking was used to investigate the interactions of OA with nine selected cancer-related protein targets. OA docked well with human 17β-hydroxysteroid dehydrogenase type-1 (17βHSD1), caspase-3, and epidermal growth factor receptor tyrosine kinase (binding affinities: -9.8, -9.3, and -9.1 kcal/mol, respectively). OA is a triterpenoid compound with structural similarity to steroids. This similarity with the substrates of 17βHSD1 gives the inhibitor candidate an excellent opportunity to bind to 17βHSD1. The structural and functional dynamics of OA-17βHSD1 were investigated by molecular dynamics simulations at 240 ns. Molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) studies showed that OA had a binding free energy that is comparable with that of vincristine (-52.76, and -63.56 kcal/mol, respectively). The average C-α root mean square of deviation (RMSD) value of OA (1.69 Å) compared with the unbound protein (2.01 Å) indicated its high stability at the protein's active site. The binding energy and stability at the active site of 17βHSD1 recorded in this study indicate that OA exhibited profound inhibitory potential. OA could be a good scaffold for developing new anti-breast cancer drugs.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0